The present invention relates generally to the field of intravascular and intraluminal catheters. More specifically, it relates to a catheter that can be introduced into the lumen of a blood vessel or other bodily organ, both for the dilatation of the lumen, and for the delivery of a therapeutic agent directly to the tissues surrounding the lumen, either simultaneously or sequentially.
In the medical procedure known as percutaneous transluminal angioplasty, or PTA (sometimes called percutaneous transluminal coronary angioplasty, or PTCA), a catheter having an expansible distal end is introduced into the lumen of a blood vessel (typically a coronary artery), with the distal end positioned in the region of a previously-located stenosis. The expansible end (typically comprising an inflatable bladder or balloon) is then expanded to dilate the vessel, thereby restoring adequate blood flow through the stenotic region.
The benefits of PTA are occasionally limited by one of two mechanisms: abrupt vessel closure, and restenosis. The former is a phenomenon characterized by a rapid and acute occlusion of the vessel within the first few hours after the PTA procedure, caused principally by arterial dissection and/or thrombosis. The result frequently is myocardial infarction, with possible death, if blood flow is not quickly restored. Restenosis is the reappearance of the stenosis within a few months after the PTA procedure, requiring a repetition of the procedure. It is currently believed that the occurrence of both of these phenomena could be substantially reduced by the introduction of suitable therapeutic agents directly to the arterial wall tissue during or immediately after the PTA procedure.
The typical methods of intravascular medication involve the delivery of the medication systemically, either intravenously, or regionally (e.g., by intracoronary infusion). Systemic delivery is usually ill-suited to the treatment of conditions occurring at one or more discrete sites, because it involves the delivery of the medication to sites other than the target site, and it requires the infusion of large doses of the medication to assure the delivery of a therapeutic dose to the target site, thereby creating the possibility of deleterious effects. Thus, the dosage that can be delivered to the target site may be limited by the need to minimize unwanted effects in other parts of the body. Furthermore, systemic delivery exposes the medication to possible degradation and elimination by the action of other bodily organs.
The aforementioned limitations of systemic delivery would be obviated by local intramural delivery of the therapeutic agent directly to the vessel wall at the target site. Accordingly, interest has been shown in the development of catheters that can deliver medication directly to a target site within a blood vessel or other bodily lumen. Typically, such prior art drug delivery catheters include a balloon at the distal end of the catheter. The balloon is introduced into the vascular lumen and located adjacent the target site, at which time it is expanded to engage the lumen wall. The balloon is provided with a porous surface, such that the pressurized liquid that expands the balloon escapes through the pores to the luminal wall surface. Thus, the pressurized liquid that expands the balloon also serves as the vehicle for the therapeutic agent.
Drug delivery catheters of the perforated balloon type do, however, have some drawbacks. For example, because the same fluid is used as the balloon inflation medium and as the drug medium, dilatation by balloon expansion is necessarily accompanied by drug delivery; neither function can be performed independently, which may be disadvantageous or inefficient in various clinical situations. Further inefficiency is engendered by the expulsion of the therapeutic agent before the balloon is fully expanded, so that the agent is not as forcefully administered to the luminal wall tissue as it would be if the balloon were fully expanded so as to bring it into close proximity or contact with the wall. A related problem is that the agent is typically expelled at relatively low pressures that are insufficient to effect any substantial degree of penetration of the lumen wall surface, thereby limiting the therapeutic effect of the agent in certain situations. Finally, in drug delivery PTA catheters in which the same fluid is used as the balloon inflation medium and the drug medium, the reversal of fluid flow to deflate the balloon may tend to draw blood into the catheter, requiring the catheter to be withdrawn for purging or replacement after a single use.
Examples of the above-described "single fluid" perforated balloon type of drug delivery dilatation catheter are disclosed in the following U.S. Pat. No. 5,087,244--Wolinsky et al.; U.S. Pat. No. 5,112,305--Barath et al.; and U.S. Pat. No. 5,344,402--Crocker.
U.S. Pat. No. 5,370,614--Amundson et al. discloses a balloon angioplasty catheter, wherein the balloon is contained within a frangible sheath. The space between the balloon and the sheath is filled with a drug-containing viscous matrix. Expansion of the balloon within a vascular lumen causes the sheath to burst, releasing the viscous matrix into the lumen. This construction requires a therapeutic agent that can be manufactured in the form of a viscous matrix, which may not be possible or practical for all desired agents. Furthermore, the available dose of the agent is limited by the volume of the space between the balloon and the sheath, a volume that is further limited by the cross-sectional area of the lumen at the target site. As with more typical "single fluid" perforated balloon infusion catheters, dilatation and infusion cannot be performed independently.
U.S. Pat. No. 4,994,033--Shockey et al. discloses a drug delivery dilatation catheter, in which an imperforate dilatation balloon is concentrically surrounded by a second expansible membrane that is perforated. While an inflation fluid is delivered to the dilatation balloon, a therapeutic agent is introduced into the space between the dilatation balloon and the perforated membrane, thereby expanding both the dilatation balloon and the perforated membrane, the latter engaging the lumen wall. The agent is thereby forced out of the perforations to bathe the lumen wall tissue. Proper delivery of the agent requires a delivery pressure sufficient to expand the outer, perforated membrane. Furthermore, the outer membrane perforations must be minute ("microholes"). This device thus requires a specialized manufacturing step, e,g., precision laser drilling, thereby adding to its cost of manufacture.
Another approach is taken by the device described in U.S. Pat. No. 5,336,178--Kaplan et al. This device comprises a multi-lumen expansible sleeve that slides over the exterior of a standard PTA balloon catheter. The lumens of the sleeve are ported at their distal ends. Inflation of the balloon at the delivery site expands the sleeve to bring the delivery ports into close proximity with the surrounding tissue, whereupon a therapeutic agent is delivered to the tissue via the sleeve lumens and their ports. While this device allows dilatation and infusion to be performed independently, in the commercially available embodiment of this device, the dilatation must be performed first, the balloon deflated, the sleeve passed over the balloon, and the balloon then reinflated before infusion commences. This procedure can result in the movement of the dilatation catheter away from the target site, thus requiring laborious repositioning of the combined dilatation and infusion catheter assembly. In addition, the distribution of the agent in this device (as in the perforated balloon-type of devices) is limited by the size, distribution, and number of holes or ports through which the agent flows into the vessel. Furthermore, the use of a multi-lumen concentric sleeve over the balloon dictates a relatively large uninflated cross-sectional area for the device, even in those embodiments (as described in the aforementioned U.S. Pat. No. 5,336,178) that do not require the inflation-deflation-reinflation procedure. This makes the device disadvantageous for use in smaller blood vessels and bodily passages, and in those vessels and passages that have highly occlusive stenoses. In addition, the rather complex structure of this device may contribute to relatively high manufacturing costs.
There has thus been a need for a drug delivery dilatation catheter that permits dilatation and drug delivery (infusion) to be performed independently. Furthermore, the need has been felt for such a device that has an uninflated or unexpanded cross-sectional area that is not significantly greater than that of an ordinary balloon-type of PTA catheter. In addition, it would be advantageous for such a device to be capable of delivering the drug at pressures sufficient to penetrate the surface of the tissue surrounding the lumen into which the catheter is placed.